The lysis of allogeneic cells by thymus-derived lymphocytes (T cells) from alloimmunized donors is a widely documented, but poorly understood, phenomenon. The proposed studies will examine several aspects of T-cell mediated lysis in a manner which, it is felt, will provide mechanistic insight into the lytic process. The lysis of 51Cr- labelled DBA/2 mastocytoma cells (P815) by lymphocytes from alloimmunized C57BL/6 mice will primarily serve as the assay system. Lysis in this system is reversibly inhibited by cytochalasin B, by prostaglandins E1 and E2 and by EDTA. Additionally, colchicine inhibits cytolysis in an irreversible manner. Because of the specificity of these inhibitors in other cell systems, T-cell mediated cytolysis may be dependent on antigen-triggered mediator synthesis and its subsequent secretion. It is proposed to test this hypothesis a) by temporally sequencing the order in which inhibitors of cytolysis act and b) by directly seeking the presence of lytic mediator. Protein synthesis may be required for cytolysis. The extent, and nature, of alloantigen- induced protein synthesis in "immune" lymphocytes will be characterized and relationships between such synthesis and cytolytic activity will be sought. If unique proteins are found to be synthesized in the presence of alloantigen, isolation will be attempted. Evidence will be sought for the transferral of material from lymphocyte to target cell.